Rapport Therapeutics Conference Call Summary Company Overview - **Company**: Rapport Therapeutics (NasdaqGM:RAPP) - **Industry**: Precision Neuroscience - **Focus**: Development of therapies for neurological conditions using receptor-associated proteins Key Points and Arguments Company Vision and Strategy - Rapport Therapeutics aims to be a leading precision neuroscience company, leveraging receptor-associated proteins to create highly specific compounds for various neurological conditions [8][9] - The company was formed through a collaboration between Third Rock and Johnson & Johnson, bringing significant institutional knowledge to its programs [9] Lead Program: RAP-219 - **Description**: RAP-219 is a novel forebrain-restricted TARP gamma-8 AMPA modulator targeting focal onset seizures [10][11] - **Financial Position**: As of September 30, 2025, the company had approximately $513 million, providing a cash runway into the second half of 2029 [10] - **Clinical Progress**: Positive phase two data for RAP-219 was released in September 2025, with plans to enter pivotal studies in Q2 2026 [10][13] Market Opportunities - **Focal Onset Seizures**: Approximately 1.8 million patients in the U.S. with a market opportunity of $15 billion [16] - **Primary Generalized Tonic-Clonic Seizures**: Around 800,000 patients with a $7 billion market opportunity [16] - **Bipolar Mania**: 1.5 million patients with a $40 billion market opportunity [16] - **Long-Acting Injectable (LAI)**: Expected to be the first of its kind in epilepsy, providing significant revenue potential [15][16] Clinical Data and Efficacy - **Phase 2A Trial Results**: - 71% median reduction in long episodes (electrographic seizures) [27] - 77.8% reduction in clinical seizures, with 72% of patients achieving a 50% reduction [28] - 24% of patients achieved clinical seizure freedom, a significant outcome compared to historical placebo rates [29] - **Tolerability**: The drug was well tolerated with a low discontinuation rate of 10% [30] Future Developments - **Bipolar Mania Study**: Expected data in the first half of 2027 [35] - **Long-Acting Injectable**: Expected to enter IND-enabling studies with initial human PK data anticipated in 2027 [34][35] - **Discovery Pipeline**: Focused on nicotinic receptors with promising candidates for chronic pain and migraine [39] Regulatory and Market Positioning - Rapport Therapeutics has received positive feedback from the FDA, allowing for accelerated development of RAP-219 [13][32] - The company is positioned to potentially lead in the market with a new mechanism of action and favorable safety profile compared to existing treatments [44][46] Additional Important Information - The company emphasizes the importance of addressing treatment-resistant patients, with 30%-40% of focal onset seizure patients being refractory to current medications [16][18] - The long-acting injectable formulation is expected to mitigate risks associated with missed doses, a significant concern for patients and caregivers [47][48] - The discovery platform aims to create a self-sustaining pipeline, moving beyond single-asset dependency [38] This summary encapsulates the key insights from the conference call, highlighting the strategic direction, clinical advancements, and market potential of Rapport Therapeutics and its lead program, RAP-219.

Rapport Therapeutics Conference Call Summary Company Overview - Rapport Therapeutics is focused on precision neuroscience, leveraging receptor-associated proteins to enhance treatment efficacy and tolerability for patients [2][3] Key Programs - The lead program, RAP-219, is a TARP gamma-8 AMPA modulator, showing promising results in epilepsy and ongoing programs in bipolar mania [2][3] - RAP-219 has demonstrated a 78% median reduction in clinical seizure frequency and a 24% seizure freedom rate in a proof of concept study [11][12] FDA Engagement and Study Plans - The company plans to meet with the FDA by the end of 2025 for an end of phase two meeting, aiming to start phase three studies by Q3 2026 [4][5] - Two parallel registrational studies are planned, following a standard protocol for focal epilepsy [4][5] Safety and Efficacy Insights - The biological thesis focuses on modulating the AMPA receptor through TARP gamma-8, which is expressed in key brain structures related to focal seizures [6][8] - The tolerability profile from phase two data showed a 10% discontinuation rate, indicating best-in-class tolerability for anti-seizure medications [9] - Concerns regarding adverse events (AEs) related to psychiatric disorders were addressed, with no significant findings in their trials [10] Patient Population and Efficacy Expectations - The proof of concept study involved a highly refractory patient population, with 70% on three or four anti-seizure medications [16] - The efficacy results are expected to translate well into the broader phase three patient population, despite potential variability [18][13] Bipolar Mania and Other Indications - The company is exploring RAP-219 for bipolar mania, supported by the drug's mechanism targeting excitatory processes in the limbic structure [24][26] - Enrollment for the bipolar trial is progressing well, with data expected in 2027 [26] Market Opportunity - The potential market opportunity for RAP-219 in epilepsy is estimated to be multi-billion dollars, with expected utilization similar to existing treatments like Keppra [29] Upcoming Milestones - Key updates expected include the end of phase two meeting with the FDA, additional data analyses at AES in December 2025, and the initiation of phase three studies in 2026 [30][31] - The company has sufficient cash reserves, approximately $500 million, to fund operations through 2029 [32]